Mouse Genome Informatics
hm1
    Tnftm2Gkl/Tnftm2Gkl
involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 5 and 12 weeks of age

immune system
• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum
• becomes severe by 4 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall
• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal
• at 6 weeks of age circulating levels of TNF are up to 822 +/- 447 pg/ml compared to undetectable levels in wild-type mice
• develop signs of chronic polyarthritis including joint swelling, distortion of fore and hind paw morphology, impaired movement
• disease onset occurs at 12 days of age
• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction
• both IgM and IgG are detected in arthritic joints

growth/size
• body weight does no exceed 6-7 g

digestive/alimentary system
• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum
• becomes severe by 4 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall

skeleton
• develop signs of chronic polyarthritis including joint swelling, distortion of fore and hind paw morphology, impaired movement
• disease onset occurs at 12 days of age
• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction
• both IgM and IgG are detected in arthritic joints

hematopoietic system
• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal

homeostasis/metabolism
• at 6 weeks of age circulating levels of TNF are up to 822 +/- 447 pg/ml compared to undetectable levels in wild-type mice

endocrine/exocrine glands
• severe hypoplasia with atrophy and disorganization of the cortical and medullary areas is seen at 4 weeks of age; however at 12 days of age the ratio of thymic and peripheral T cell subsets is normal

Mouse Models of Human Disease
OMIM IDRef(s)
Rheumatoid Arthritis; RA 180300 J:54056


Mouse Genome Informatics
ht2
    Tnftm2Gkl/Tnf+
involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• elevated chronic and acute inflammatory indices
• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum (J:54056)
• becomes severe by 8 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall (J:54056)
• by 4-7 months of age complete loss of villous structure and rudimental granulomata are seen (J:54056)
• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei (J:92307)
• mutants on a high-fat diet develop accelerated onset of intestinal inflammation compared to wild-type mice (J:204922)
• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice
• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum
• at 4 weeks of age, fewer CD8alpha alpha intraepithelial lymphocytes are present in the ileum
• however, no significant difference is seen in the number of CD8alpha beta intraepithelial lymphocytes
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers
• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets
• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum
• mutants show increased Th17-biased lymphocyte infiltration into the lamina propria of the ileum on a high-fat diet compared to wild-type mice
• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice
• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice (J:54056)
• TNF plasma levels are increased at 12 weeks of age in mutants compared to wild-type mice, however high-fat diet does not result in a further increase (J:204922)
• expression analysis indicates that mutants do not show adipose tissue inflammation when fed a high-fat diet as seen in wild-type mice
• Background Sensitivity: at 9 months arthritis is severe enough to reduce mobility unlike in mice on a mixed background including SPRET/Ei (J:92307)
• at 9 months joints show extensive lymphocytic infiltration, thickening of the synovial lining, pannus formation, and abnormal ingrowth of the synovial lining (J:92307)

digestive/alimentary system
• mutants show elevated fecal energy content when fed a high-fat diet, suggesting steatorrhea, which is not seen in wild-type mice
• mutants show increased intestinal permeability when fed a high-fat diet
• elevated chronic and acute inflammatory indices
• first detected between 2 and 4 weeks of age as mucosal abnormalities with intestinal villous blunting and broadening generally confined to the terminal ileum (J:54056)
• becomes severe by 8 weeks, with increased numbers of submucosal lymphoid aggregates and follicles eventually penetrating deep into the muscular layers of the bowel wall (J:54056)
• by 4-7 months of age complete loss of villous structure and rudimental granulomata are seen (J:54056)
• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei (J:92307)
• mutants on a high-fat diet develop accelerated onset of intestinal inflammation compared to wild-type mice (J:204922)

skeleton
• Background Sensitivity: at 9 months arthritis is severe enough to reduce mobility unlike in mice on a mixed background including SPRET/Ei (J:92307)
• at 9 months joints show extensive lymphocytic infiltration, thickening of the synovial lining, pannus formation, and abnormal ingrowth of the synovial lining (J:92307)

homeostasis/metabolism
• mutants do not develop obesity on a high-fat diet as seen in wild-type mice
• mutants on a high-fat diet do not show increased fat depots or enlarged adipocytes as seen in wild-type mice
• mutants on high-fat diet do not exhibit an increase in plasma leptin levels as seen in wild-type mice
• mutants exhibit increased plasma CCL20 levels on both a regular or high-fat diet compared to wild-type mice
• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice (J:54056)
• TNF plasma levels are increased at 12 weeks of age in mutants compared to wild-type mice, however high-fat diet does not result in a further increase (J:204922)
• glucose homeostasis remains normal in mutants fed a high-fat diet unlike in wild-type mice which show impaired glucose tolerance and elevated fasting blood glucose

hematopoietic system
• mutants show higher numbers of CD11c+ dendritic cells in the ileal lamina propria when fed a high-fat diet compared to wild-type mice
• at 16 weeks of age, the CD8alpha alpha to CD8alpha beta ratio is significantly decreased in the lamina propria of the ileum
• at 4 weeks of age, fewer CD8alpha alpha intraepithelial lymphocytes are present in the ileum
• however, no significant difference is seen in the number of CD8alpha beta intraepithelial lymphocytes
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers
• increase in the number of TNF-producing cells in the lamina propria and intraepithelial lymphocyte subsets
• reduced expression of interferon gamma and increased expression of interleukin 17 and 10 in CD4+ lymphocytes in the lamina propria of the ileum
• mutants show increased Th17-biased lymphocyte infiltration into the lamina propria of the ileum on a high-fat diet compared to wild-type mice

integument
• at 9 months of age

behavior/neurological
• mutants exhibit increased energy intake on a high-fat diet

growth/size
• mutants do not develop obesity on a high-fat diet as seen in wild-type mice
• mutants on a high-fat diet do not show increased fat depots or enlarged adipocytes as seen in wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Rheumatoid Arthritis; RA 180300 J:54056


Mouse Genome Informatics
ht3
    Tnftm2Gkl/Tnf+
involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• bilaterial inflammation of the sacroiliac joints occurs starting at 4 weeks of age
• the fibrocartilagenous portion of the joint is invaded by mononuclear cells that protrude into the bone marrow

skeleton
• bilaterial inflammation of the sacroiliac joints occurs starting at 4 weeks of age
• the fibrocartilagenous portion of the joint is invaded by mononuclear cells that protrude into the bone marrow


Mouse Genome Informatics
ht4
    Tnftm2Gkl/Tnf+
involves: 129S/SvEv * C57BL/6 * SPRET/Ei
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei
• Background Sensitivity: at 9 months arthritis is not severe enough to reduce mobility unlike in mice on a mixed background that does not include SPRET/Ei

digestive/alimentary system
• at 9 months similar bowel inflammation extending into the mucosal layers and loss of crypt morphology is seen in mice on a mixed background with or without SPRET/Ei

skeleton
• Background Sensitivity: at 9 months arthritis is not severe enough to reduce mobility unlike in mice on a mixed background that does not include SPRET/Ei

integument
• at 9 months of age


Mouse Genome Informatics
ht5
    Tnftm2Gkl/Tnf+
involves: 129S/SvEv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mice display high levels of apoptosis in the ilea at 3 months of age

immune system
• inflammatory bowel disease develops between 4-8 weeks of age
• there is a significant increase in CD8+ T cell number in Tnftm2Gkl mice past 2 months of age
• splenocyte counts past 2 months of age show increases in CD11b+ myeloid cells
• mild splenomegaly development correlates with inflammatory bowel disease (IBD) development and becomes significant by 4 months of age
• T lymphocytes show a high degree of target cell lysis of syngeneic targets
• in allogeneic mixed lymphocyte reactions, splenocytes show enhanced proliferation compared to wild-type controls
• when lethality irradiated heterozygotes (that had also received anti-Tnf antibody treatment) receive bone marrow from wild-type mice only display mild villus blunting 9 weeks after removal of antibody treatment

hematopoietic system
• there is a significant increase in CD8+ T cell number in Tnftm2Gkl mice past 2 months of age
• splenocyte counts past 2 months of age show increases in CD11b+ myeloid cells
• mild splenomegaly development correlates with inflammatory bowel disease (IBD) development and becomes significant by 4 months of age
• T lymphocytes show a high degree of target cell lysis of syngeneic targets
• in allogeneic mixed lymphocyte reactions, splenocytes show enhanced proliferation compared to wild-type controls

digestive/alimentary system
• inflammatory bowel disease develops between 4-8 weeks of age


Mouse Genome Informatics
ht6
    Tnftm1Gkl/Tnftm2Gkl
involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice
• increased basal and LPS-induced secretion of TNF from thioglycollate-elicited peritoneal macrophages and bone marrow-derived macrophages
• spleen derived T lymphocytes have 3-fold greater TNF production and prolonged mRNA accumulation after incubation with an agonistic anti-CD3 antibody
• splenic B220+ cells also show increased basal and mitogen-stimulated TNF production
• primary synovial and lung fibroblasts display spontaneous TNF secretion and increased secretion following LPS stimulation unlike controls
• disease onset occurs at 6-8 weeks of age
• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction
• both IgM and IgG are detected in arthritic joints
• increased sensitivity to LPS-induced mortality with 5 of 10 dying after injection of 100 ug/ 25 g compared to complete survival of control mice at the same dose

skeleton
• disease onset occurs at 6-8 weeks of age
• early signs include hyperplasia of the synovial membrane and the presence of polymorphonuclear infiltrates; progressing to pannus and fibrous tissue formation, subchondral bone erosion, and articular cartilage destruction
• both IgM and IgG are detected in arthritic joints

homeostasis/metabolism
• at 6 weeks of age circulating levels of TNF are up between 90 and 430 pg/ml compared to undetectable levels in wild-type mice

Mouse Models of Human Disease
OMIM IDRef(s)
Rheumatoid Arthritis; RA 180300 J:54056


Mouse Genome Informatics
cn7
    Tg(Col6a1-cre)1Gkl/?
Tnftm2Gkl/Tnf+
Tnfrsf1atm2Gkl/Tnfrsf1atm2Gkl

involves: 129S/SvEv * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• the ileum contains inflammatory pathology reminiscent of Crohn's disease
• pathology includes blunting of intestinal villi, and infiltration of inflammation cells into the mucosal and submucosal layers
• 100% of mice have disease by 8 weeks of age

immune system
• the ileum contains inflammatory pathology reminiscent of Crohn's disease
• pathology includes blunting of intestinal villi, and infiltration of inflammation cells into the mucosal and submucosal layers
• 100% of mice have disease by 8 weeks of age
• 100% of mice have arthritis by 8 weeks of age
• joints are infiltrated by mononuclear cells
• mice also develop spondyloarthritis in their sacroiliac joints

skeleton
• 100% of mice have arthritis by 8 weeks of age
• joints are infiltrated by mononuclear cells
• mice also develop spondyloarthritis in their sacroiliac joints


Mouse Genome Informatics
cx8
    Mapk11tm1Jsca/Mapk11tm1Jsca
Tnftm2Gkl/Tnf+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• onset and severity of inflammation of the terminal ileum are similar to mice heterozygous for the Tnf allele only
• onset and severity of arthritis are similar to mice heterozygous for the Tnf allele only

digestive/alimentary system
• onset and severity of inflammation of the terminal ileum are similar to mice heterozygous for the Tnf allele only

skeleton
• onset and severity of arthritis are similar to mice heterozygous for the Tnf allele only


Mouse Genome Informatics
cx9
    Tnftm2Gkl/Tnftm2Gkl
Tnfrsf1atm1Blt/Tnfrsf1atm1Blt

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 6 weeks of age circulating levels of TNF are 320 +/- 160 pg/ml in disease free mutants compared to undetectable levels in wild-type mice
• however, no signs of arthritis or inflammatory bowel disease are detected
• increased basal and LPS-induced secretion of TNF from thioglycollate-elicited peritoneal macrophages and bone marrow-derived macrophages
• primary synovial and lung fibroblasts display spontaneous TNF secretion and increased secretion following LPS stimulation unlike controls

homeostasis/metabolism
• at 6 weeks of age circulating levels of TNF are 320 +/- 160 pg/ml in disease free mutants compared to undetectable levels in wild-type mice
• however, no signs of arthritis or inflammatory bowel disease are detected


Mouse Genome Informatics
cx10
    Tcrdtm1Mom/Tcrdtm1Mom
Tnftm2Gkl/Tnf+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls

digestive/alimentary system
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls


Mouse Genome Informatics
cx11
    Mapkapk2tm1Mgl/Mapkapk2tm1Mgl
Tnftm2Gkl/Tnf+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• increase in mortality from 8 weeks of age onward

cellular
• mice have fewer apoptotic cells in inflamed ileal tissue compared to Tnftm2Gkl/+ controls

immune system
N
• there is no change in CD4+ to CD8+ ratios compared to findings in Tnftm2Gkl/+ single mutants (J:108572)
• Tnftm2Gkl phenotype is exacerbated in these mice
• IBD is associated with early formation of multiple granulomas

digestive/alimentary system
• Tnftm2Gkl phenotype is exacerbated in these mice


Mouse Genome Informatics
cx12
    Map3k8tm1Pnt/Map3k8tm1Pnt
Tnftm2Gkl/Tnf+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• there is a delayed onset and significant attenuation of disease compared to controls
• there is a significant increase in numbers of CD4+ and CD8+ cells
• number of CD8+CD44hi T cells is higher than in Tnftm2Gkl/+ controls

hematopoietic system
• there is a significant increase in numbers of CD4+ and CD8+ cells
• number of CD8+CD44hi T cells is higher than in Tnftm2Gkl/+ controls

digestive/alimentary system
• there is a delayed onset and significant attenuation of disease compared to controls


Mouse Genome Informatics
cx13
    Mapk9tm1Flv/Mapk9tm1Flv
Tnftm2Gkl/Tnf+

involves: 129P2/OlaHsd * 129S/SvEv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• mice have significantly higher numbers of apoptotic cells in the ilea compared to lower numbers in the infiltrate indicating a higher rate of apoptosis

immune system
N
• there is no change in CD4+ to CD8+ ratios compared to findings in Tnftm2Gkl/+ single mutants (J:108572)
• there is a delayed onset and significant attenuation of disease

digestive/alimentary system
• there is a delayed onset and significant attenuation of disease


Mouse Genome Informatics
cx14
    Il12btm1Jm/Il12btm1Jm
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice display delayed development and attenuation of inflammatory bowel disease

digestive/alimentary system
• mice display delayed development and attenuation of inflammatory bowel disease


Mouse Genome Informatics
cx15
    Tnftm2Gkl/Tnf+
Tnfrsf1btm1Mwm/Tnfrsf1btm1Mwm

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 1-5 months of age, only mild intestinal inflammation and no signs of transmural inflammation are seen, unlike in mice heterozygous for Tnftm2Gkl only
• arthritis is more aggressive and destructive than in mice heterozygous for Tnftm2Gkl only with increased swelling of the joints, synovial hyperplasia, numbers of polymorphonuclear infiltrates, and destruction of bone and cartilage

digestive/alimentary system
• at 1-5 months of age, only mild intestinal inflammation and no signs of transmural inflammation are seen, unlike in mice heterozygous for Tnftm2Gkl only

skeleton
• arthritis is more aggressive and destructive than in mice heterozygous for Tnftm2Gkl only with increased swelling of the joints, synovial hyperplasia, numbers of polymorphonuclear infiltrates, and destruction of bone and cartilage


Mouse Genome Informatics
cx16
    Ccl25tm1Mal/Ccl25tm1Mal
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• develop inflammatory bowl disease with similar onset, progression, and severity as in littermates heterozygous for both alleles
• elevated acute and chronic inflammatory indices similar to littermates heterozygous for both alleles
• decrease in the CD8alpha alpha to CD8alpha beta ratio similar to that in mice heterozygous for Tnftm2Gkl alone
• more pronounced decrease in this subset early in the inflammatory disease process compared to mice heterozygous for Tnftm2Gkl alone
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers similar to mice heterozygous for Tnftm2Gkl alone

digestive/alimentary system
• develop inflammatory bowl disease with similar onset, progression, and severity as in littermates heterozygous for both alleles
• elevated acute and chronic inflammatory indices similar to littermates heterozygous for both alleles

hematopoietic system
• decrease in the CD8alpha alpha to CD8alpha beta ratio similar to that in mice heterozygous for Tnftm2Gkl alone
• more pronounced decrease in this subset early in the inflammatory disease process compared to mice heterozygous for Tnftm2Gkl alone
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers similar to mice heterozygous for Tnftm2Gkl alone


Mouse Genome Informatics
cx17
    Ccr9tm1.1Mal/Ccr9tm1.1Mal
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• develop inflammatory bowl disease with similar onset, progression, and severity as in littermates heterozygous for both alleles
• elevated acute and chronic inflammatory indices similar to littermates heterozygous for both alleles
• decrease in the CD8alpha alpha to CD8alpha beta ratio similar to that in mice heterozygous for Tnftm2Gkl alone
• more pronounced decrease in this subset early in the inflammatory disease process compared to mice heterozygous for Tnftm2Gkl alone
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers similar to mice heterozygous for Tnftm2Gkl alone

digestive/alimentary system
• develop inflammatory bowl disease with similar onset, progression, and severity as in littermates heterozygous for both alleles
• elevated acute and chronic inflammatory indices similar to littermates heterozygous for both alleles

hematopoietic system
• decrease in the CD8alpha alpha to CD8alpha beta ratio similar to that in mice heterozygous for Tnftm2Gkl alone
• more pronounced decrease in this subset early in the inflammatory disease process compared to mice heterozygous for Tnftm2Gkl alone
• decrease in TCRalpha beta CD8alpha alpha and TCRalpha beta CD8alpha alpha CD4 numbers similar to mice heterozygous for Tnftm2Gkl alone


Mouse Genome Informatics
cx18
    B2mtm1Jae/B2mtm1Jae
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• mice display delayed development and attenuation of inflammatory bowel disease

digestive/alimentary system
• mice display delayed development and attenuation of inflammatory bowel disease


Mouse Genome Informatics
cx19
    Cd4tm1Mak/Cd4tm1Mak
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• there is high incidence of mortality in mice by age of 2-3 months

immune system
• mice show exacerbation of IBD compared to Tnftm2Gkl/+ mice

digestive/alimentary system
• mice show exacerbation of IBD compared to Tnftm2Gkl/+ mice


Mouse Genome Informatics
cx20
    Ighmtm1Cgn/Ighmtm1Cgn
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S2/SvPas * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls

digestive/alimentary system
• development and severity of inflammatory bowel disease are similar to Tnftm2Gkl/+, wild-type B2m controls


Mouse Genome Informatics
cx21
    Rag1tm1Mom/Rag1tm1Mom
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• only minimal intestinal inflammation is seen, unlike in mice heterozygous for Tnftm2Gkl only
• arthritis is similar to mice heterozygous for Tnftm2Gkl only

digestive/alimentary system
• only minimal intestinal inflammation is seen, unlike in mice heterozygous for Tnftm2Gkl only

skeleton
• arthritis is similar to mice heterozygous for Tnftm2Gkl only


Mouse Genome Informatics
cx22
    Ifngtm1Ts/Ifngtm1Ts
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * 129S7/SvEvBrd * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• development and severity of IBD are similar to Tnftm2Gkl/+, wild-type Ifng controls

digestive/alimentary system
• development and severity of IBD are similar to Tnftm2Gkl/+, wild-type Ifng controls


Mouse Genome Informatics
cx23
    Itgb7tm1Cgn/Itgb7tm1Cgn
Tnftm2Gkl/Tnf+

involves: 129S/SvEv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• significant attenuation of the inflammatory bowel disease pathology with reduced acute and chronic inflammatory indices relative to mice heterozygous for Tnftm2Gkl alone
• chronic inflammatory arthritis is similar to mice heterozygous for Tnftm2Gkl alone

skeleton
• chronic inflammatory arthritis is similar to mice heterozygous for Tnftm2Gkl alone